Pharmacology · Class
Hepatitis C direct-acting antivirals !
Oral combinations that cure more than 95% of people with hepatitis C in a few weeks. They block three viral proteins: NS3/4A, NS5A and NS5B.
Updated 2026-11-01
What they are
Oral drugs that act directly on hepatitis C virus proteins and, combined, cure more than 95% of people, usually in 12 to 24 weeks (WHO). Pangenotypic combinations (sofosbuvir-velpatasvir, glecaprevir-pibrentasvir) work against all genotypes, which makes testing and treatment simpler. Generic versions have made the course cheap in many low- and middle-income countries. There is no vaccine against hepatitis C.
Mechanism of action
Each group blocks a different step of viral replication. NS5B polymerase inhibitors (sofosbuvir, a nucleotide) are built into the new viral RNA and stop it. NS5A inhibitors (velpatasvir, ledipasvir, pibrentasvir, daclatasvir) block a protein needed to build the replication complex and assemble virions. NS3/4A protease inhibitors (glecaprevir, grazoprevir, voxilaprevir) prevent the cutting of the viral polyprotein into working proteins. Two or three groups are combined so that resistance does not appear.
Target: HCV NS5B polymerase, NS5A protein and NS3/4A protease
Drugs in this class
- SofosbuvirThe backbone of most hepatitis C regimens. It blocks the virus's RNA polymerase and is always combined with another…Hepatitis C virus NS5B RNA polymerase
- Sofosbuvir + velpatasvirA pangenotypic pill for hepatitis C that WHO recommends; it cures most patients without the need to know the genotype.Hepatitis C virus NS5B polymerase (sofosbuvir) and NS5A protein (velpatasvir)
- Ledipasvir + sofosbuvirA single-tablet hepatitis C combination for genotypes 1, 4, 5 and 6. It joins an NS5A inhibitor with the NS5B…Hepatitis C virus NS5A protein (ledipasvir) and NS5B polymerase (sofosbuvir)
- Glecaprevir + pibrentasvirA pangenotypic hepatitis C combination of an NS3/4A protease inhibitor and an NS5A inhibitor, taken with food.Hepatitis C virus NS3/4A protease (glecaprevir) and NS5A protein (pibrentasvir)
Others in the class
- Daclatasvir
- Ravidasvir
- Elbasvir-grazoprevir
- Sofosbuvir-velpatasvir-voxilaprevir
Test yourself
Think of the answer, then tap the question to see it.
Which three hepatitis C proteins do direct-acting antivirals target?
The NS3/4A protease, the NS5A protein and the NS5B RNA polymerase.
What test is done before any direct-acting antiviral, and why?
Hepatitis B testing (HBsAg, anti-HBc): HBV can reactivate as hepatitis C is cleared.
Which antiarrhythmic must not be combined with sofosbuvir?
Amiodarone: the combination can cause severe symptomatic bradycardia.
What does «pangenotypic» mean?
Active against all hepatitis C genotypes, so treatment can start without genotyping.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Hepatitis C (World Health Organization, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 63 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.